In the manufacture of pharmaceutical formulations for oral administration, it may be desirable for the drug to dissolve rapidly soon after administration. However, it is known that certain physic-chemical properties of the drug, such as particle size, wettability, or solubility, may lead to a pharmaceutical formulation which exhibits unsatisfactory and/or variable dissolution or to a formulation which exhibits unsatisfactory and/or variable bioavailability. Such formulations may be unsuitable for use by patients.
Compound I (below) is disclosed in international patent application
for use in the treatment of cancer.
Javaid et al (J. Pharm. Sci. 61 (9) 1972 pp 1370-1373) studied the effect of various classes of buffering agents on the dissolution of aspirin from tablet formulations. Compound I is currently in clinical studies for the treatment of cancer, in particular cancers of the lung, breast, gatric and bladder. Dosing is currently done with orally delivered tablets with tablet strengths of 20 and 100 mg. These tablets exhibit satisfactory dissolution across the physiological pH range. However, the manufacturing process used for clinical batches cannot be operated at commercial scale, due to a high incidence of filming which cannot be corrected using conventional means. It is desirable, therefore, to produce new pharmaceutical formulations of Compound I which overcome at least in part the above problems.